miR-450a Acts as a Tumor Suppressor in Ovarian Cancer by Regulating Energy Metabolism

Muys, Bruna Rodrigues; Sousa, Josane F.; Plaça, Jéssica Rodrigues; Araújo, Luíza Ferreira de; Sarshad, Aishe A.; Anastasakis, Dimitrios G.; Wang, Xiantao; Li, Xiao Ling; Molfetta, Greice Andreotti de; Ramão, Anelisa; Lal, Ashish; Vidal, Daniel Onofre; Hafner, Markus; Silva, Wilson A.

doi:10.1158/0008-5472.can-19-0490

Cited by 57 publications

(43 citation statements)

References 45 publications

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“…We noticed that the in vivo effects are more pronounced than the in vitro effects in bladder cancer. Several studies (35)(36)(37)(38) have shown a similar pattern. One of the possible reasons is that we used transient transfected bladder cancer cells for in vitro assays, whereas steady transfected bladder cancer cells were used for in vivo experiments.…”

Section: Discussionsupporting

confidence: 54%

LncRNA GClnc1 promotes proliferation and invasion of bladder cancer through activation of MYC

Zhuang

et al. 2019

FASEB j.

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Various studies demonstrate that long noncoding RNAs (IncRNAs) act as oncogenes or tumor suppressors in cancer. However, the function of IncRNAs in bladder cancer still remains largely unknown. In this study, we identified an IncRNA, gastric cancer–associated IncRNA1 (GClnc1), which was in high abundance in bladder cancer tissues and its expression was related to poor survival rates in patients with bladder cancer. In vitro and in vivo assays showed that GClnc1 significantly promoted cell proliferation, metastasis, and invasiveness in bladder cancer. Mechanistically, we first found that GClnc1 bound to LIN28B and promoted the expression of myelocytomatosis proto‐oncogene (MYC) through the LIN28B/let‐7a/MYC pathway. In short, GClnc1 is clinically, functionally, and mechanistically oncogenic in bladder cancer. GClnc1 may be a potential target for treating patients with bladder cancer.—Zhuang, C., Ma, Q., Zhuang, C., Ye, J., Zhang, F., Gui, Y. LncRNA GClnc1 promotes proliferation and invasion of bladder cancer through activation of MYC. FASEB J. 33, 11045–11059 (2019). http://www.fasebj.org

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Section: Discussionsupporting

confidence: 54%

LncRNA GClnc1 promotes proliferation and invasion of bladder cancer through activation of MYC

Zhuang

et al. 2019

FASEB j.

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“…Besides, another study revealed that there were 17 differentially expressed miRNAs in metastatic OC, among which miR-21, miR-150, and miR-146a were upregulated in metastatic OC tumors [7]. Meanwhile, it was documented that miR-450a could restrain OC cell metastasis by targeting various mitochondrial mRNAs [8]. Moreover, the dysregulated miRNAs may act as novel oncogenes or anti-oncogenes in OC by regulating target genes [9].…”

Section: Introductionmentioning

confidence: 99%

Identification of Differentially Expressed microRNAs in Metastatic Ovarian Cancer

Zhang

2020

Preprint

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Background: The molecular mechanisms of ovarian cancer (OC) remain unclear. We sought to comprehensively identify microRNAs (miRNAs) that are aberrantly expressed in metastatic OC. Methods: Differentially expressed miRNAs were screened from six pairs of primary and metastatic OC tissues; their possible functions were analyzed and target genes were predicted by bioinformatics. Then gene expression profiling results were established by reverse transcription quantitative polymerase chain reaction and western blot. Targeting relationship between miR-7-5p and TGFβ2 was validated by dual-luciferase reporter assay. CCK-8, Transwell assay, scratch test and flow cytometry were used for cell function detection after miR-7-5p overexpression. Results: Twelve miRNAs and 10 target mRNAs were differentially expressed in primary and metastatic OC tissues. ITGB3, TGFβ2 and TNC correlated to miRNA function in metastatic OC. Among all 7 miRNAs, expression of hsa-miR-141-3p, hsa-miR-7-5p, hsa-miR-187-5p, hsa-miR-200a-3p, and hsa-miR-200b-3p in metastatic OC tissues was obviously lower than that in primary OC tissues ( p < 0.05). Moreover, there was a significant correlation between hsa-miR-7-5p and TGFβ2 in OC tissues. Dual-luciferase reporter assay confirmed that hsa-miR-7-5p negatively targeted TGFβ2. After miR-7-5p overexpression, the OC cell viability and invasion were reduced, the cell cycle was blocked ( p < 0.05). Conclusions: Hsa-miR-141-3p, hsa-miR-187-5p, hsa-miR-7-5p, hsa-miR-200a-3p, and hsa-miR-200b-3p expression was prominently lower in metastatic OC than in primary OC, while TGFβ2 expression was markedly increased in metastatic OC tissues. Hsa-miR-7-5p bound to TGFβ2 3’-UTR to inhibit its expression. Hsa-miR-7-5p targeted TGFβ2 to inhibit cell proliferation, invasion and cell cycle entry.

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“…Furthermore, specific target analysis carried out in ovarian cancer cell lines revealed that ACO2 transcript is a potential direct target for miR-450a, which could explain the observed decrease in glutamate production and increase in glutamine consumption by miR-450a, since ACO2 converts citrate into isocitrate, regulating the Krebs cycle and glutaminolysis. Finally, overexpression of miR-450a induced a reduction in cell migration and invasion, while tumor growth was reduced in a murine xenograft model, suggesting that miR-450a acts as a tumor suppressor [106] ( Figure 2).…”

Section: Mir-450amentioning

confidence: 99%

Non-Coding RNAs as Key Regulators of Glutaminolysis in Cancer

Ortiz-Pedraza

Muñoz-Bello

Olmedo-Nieva

et al. 2020

IJMS

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Cancer cells exhibit exacerbated metabolic activity to maintain their accelerated proliferation and microenvironmental adaptation in order to survive under nutrient-deficient conditions. Tumors display an increase in glycolysis, glutaminolysis and fatty acid biosynthesis, which provide their energy source. Glutamine is critical for fundamental cellular processes, where intermediate metabolites produced through glutaminolysis are necessary for the maintenance of mitochondrial metabolism. These include antioxidants to remove reactive oxygen species, and the generation of the nonessential amino acids, purines, pyrimidines and fatty acids required for cellular replication and the activation of cell signaling. Some cancer cells are highly dependent on glutamine consumption since its catabolism provides an anaplerotic pathway to feed the Krebs cycle. Intermediate members of the glutaminolysis pathway have been found to be deregulated in several types of cancers and have been proposed as therapeutic targets and prognostic biomarkers. This review summarizes the main players in the glutaminolysis pathway, how they have been found to be deregulated in cancer and their implications for cancer maintenance. Furthermore, non-coding RNAs are now recognized as new participants in the regulation of glutaminolysis; therefore, their involvement in glutamine metabolism in cancer is discussed in detail.Int. J. Mol. Sci. 2020, 21, 2872 2 of 26 an increased glucose consumption in relation to normal differentiated tissues. Now we know that glutamine metabolism is as important as glucose metabolism for the production of macromolecules in cancer [1].Glutamine is an abundant amino acid involved in energy production, homeostasis in pro/antioxidant species and the activation of signaling pathways in cancer. In addition to the antioxidant glutathione (GSH), nucleotides, lipids and amino acids are formed from glutamine metabolism. All of these are needed for many metabolic functions such as growth, proliferation, cell survival and defense against oxidative stress [2]. Glutamine contributes, with reduced nitrogen, to the de novo biosynthesis of diverse nitrogen-containing compounds, such as purine and pyrimidine nucleotides, glucosamine-6-phosphate and nonessential amino acids.As glutamine is the most abundant amino acid in the blood and muscle tissue, normal proliferating cells use glutamine metabolism as an energy source, mediated by its catabolic products, glutamate and α-ketoglutarate (α-kG), the latter being an intermediate of the tricarboxylic acid cycle (TCA) or Krebs cycle [3]. In 1950, Harry Eagle observed that HeLa tumor cells require an excess of glutamine, in relation to other amino acids in the culture medium, for optimal growth. Furthermore, it has been reported that tumors consume glutamine faster than the surrounding normal tissue [4]. Moreover, most cancer cells are dependent on glutamine being unable to survive under glutamine starvation, an effect that has been termed glutamine addiction [5]. Various types of cancers are high...

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miR-450a Acts as a Tumor Suppressor in Ovarian Cancer by Regulating Energy Metabolism

Cited by 57 publications

References 45 publications

LncRNA GClnc1 promotes proliferation and invasion of bladder cancer through activation of MYC

LncRNA GClnc1 promotes proliferation and invasion of bladder cancer through activation of MYC

Identification of Differentially Expressed microRNAs in Metastatic Ovarian Cancer

Non-Coding RNAs as Key Regulators of Glutaminolysis in Cancer

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